Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses

[Image: see text] The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhi...

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Autores principales: Davey, Martin S., Malde, Roshni, Mykura, Rory C., Baker, Alfie T., Taher, Taher E., Le Duff, Cécile S., Willcox, Benjamin E., Mehellou, Youcef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493972/
https://www.ncbi.nlm.nih.gov/pubmed/29457898
http://dx.doi.org/10.1021/acs.jmedchem.7b01824
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author Davey, Martin S.
Malde, Roshni
Mykura, Rory C.
Baker, Alfie T.
Taher, Taher E.
Le Duff, Cécile S.
Willcox, Benjamin E.
Mehellou, Youcef
author_facet Davey, Martin S.
Malde, Roshni
Mykura, Rory C.
Baker, Alfie T.
Taher, Taher E.
Le Duff, Cécile S.
Willcox, Benjamin E.
Mehellou, Youcef
author_sort Davey, Martin S.
collection PubMed
description [Image: see text] The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of Vγ9/Vδ2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics.
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spelling pubmed-64939722019-05-02 Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses Davey, Martin S. Malde, Roshni Mykura, Rory C. Baker, Alfie T. Taher, Taher E. Le Duff, Cécile S. Willcox, Benjamin E. Mehellou, Youcef J Med Chem [Image: see text] The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of Vγ9/Vδ2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics. American Chemical Society 2018-02-19 2018-03-08 /pmc/articles/PMC6493972/ /pubmed/29457898 http://dx.doi.org/10.1021/acs.jmedchem.7b01824 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Davey, Martin S.
Malde, Roshni
Mykura, Rory C.
Baker, Alfie T.
Taher, Taher E.
Le Duff, Cécile S.
Willcox, Benjamin E.
Mehellou, Youcef
Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
title Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
title_full Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
title_fullStr Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
title_full_unstemmed Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
title_short Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
title_sort synthesis and biological evaluation of (e)-4-hydroxy-3-methylbut-2-enyl phosphate (hmbp) aryloxy triester phosphoramidate prodrugs as activators of vγ9/vδ2 t-cell immune responses
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493972/
https://www.ncbi.nlm.nih.gov/pubmed/29457898
http://dx.doi.org/10.1021/acs.jmedchem.7b01824
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